In order to fully understand the Structure-Activity-Relationship of the butyrophenone class of antipsychotics the significance of conformational isomers must be defined. One approach to investigating conformational isomerism has been the synthesis of rigid or semi-rigid molecules which fix one of the many possible conformations. The semi-rigid conformations are then pharmacologically evaluated in animals to determine the contribution this isomer would make to the overall activity. The objective of this proposal is to study conformational isomers of butyrophenones by synthesizing semi-rigid analogs based on the quinolizidine ring. The 2-aryl-2-hydroxy-8-(o-fluorobenzoyl) -quinolizidines will be synthesized, the isomers separated and identified. These compounds will be evaluated in mice and rats by comparison with haloperidol, a butyrophenone, and ranked in order of increasing antipsychotic-like activity. The animal tests used will be those most characteristic of identifying antipsychotic activity.